Methods to understand and predict the activities--and, therefore, abuse potential--of several related classes of psychotropic drugs will be developed. It has been established by previous investigations from our laboratories that the most potent hallucinogenic drugs--LSD, and certain substituted amphetamines, phenethylamines, and tryptamines--not only have gross topographical features in common, but have very similar electronic structures, as revealed by photoelectron spectroscopic measurements of ionization potentials. This work will build on these observations: by establishing experimentally the electronic structures (orbital energies and electron distributions) of known and potential drugs of abuse (supplied to us by collaborating medicinal chemists) including hallucinogens, narcotics, and tranquilizers, and by combining this information with that obtained by studies of molecular geometries (by X-ray and computer graphics) and charge densities (by 13 C nmr), and with literature data on conformations and lipophilicities of drugs of abuse, we will develop quantitative structure-activity relationships (QuaSAR). These will be of use in the understanding of the mechanisms of action of these compounds, and in the prediction of new compounds that have significant potential for abuse in society. The long-range utility of this research will be in the design of antagonists to abused drugs and in the reliable prediction (before public discovery) of the new compounds which will have physiological activities inviting abuse by society. The exact classes of compounds to be investigated are lysergates, tryptamines, amphetamines, phenethylamines, analgesics and their antagonists, enkephalins, phencyclidines, tricyclic antidepressants, and cannabinoids, all of which have in common an essential substituted aromatic moiety and usually (except for cannabinoids) a basic amino function.